Intervertebral Disc Puncture and Treatment System

ABSTRACT

A pre-assembled, telescoping needle system comprising an outer needle surrounding a finer gauge needle which, after percutaneous penetration by the outer needle, extends to penetrate the intervertebral disc into which the injectable is to be delivered.

BACKGROUND OF THE INVENTION

The natural intervertebral disc contains a jelly-like nucleus pulposussurrounded by a fibrous annulus fibrosus. Under an axial load, thenucleus pulposus compresses and radially transfers that load to theannulus fibrosus. The laminated nature of the annulus fibrosus providesit with a high tensile strength and so allows it to expand radially inresponse to this transferred load.

In a healthy intervertebral disc, cells within the nucleus pulposusproduce an extracellular matrix (ECM) containing a high percentage ofproteoglycans. These proteoglycans contain sulfated functional groupsthat retain water, thereby providing the nucleus pulposus with itscushioning qualities. These nucleus pulposus cells may also secretesmall amounts of cytokines as well as matrix metalloproteinases(“MMPs”). These cytokines and MMPs help regulate the metabolism of thenucleus pulposus cells.

In some instances of disc degeneration disease (DDD), gradualdegeneration of the intervertebral disc is caused by mechanicalinstabilities in other portions of the spine. In these instances,increased loads and pressures on the nucleus pulposus cause the cells toemit larger than normal amounts of the above-mentioned cytokines. Inother instances of DDD, genetic factors, such as programmed cell death,or apoptosis can also cause the cells within the nucleus pulposus toemit toxic amounts of these cytokines and MMPs. In some instances, thepumping action of the disc may malfunction (due to, for example, adecrease in the proteoglycan concentration within the nucleus pulposus),thereby retarding the flow of nutrients into the disc as well as theflow of waste products out of the disc. This reduced capacity toeliminate waste may result in the accumulation of high levels of toxins.

As DDD progresses, the toxic levels of the cytokines present in thenucleus pulposus begin to degrade the extracellular matrix. Inparticular, the MMPs (under mediation by the cytokines) begin cleavingthe water-retaining portions of the proteoglycans, thereby reducingtheir water-retaining capabilities. This degradation leads to a lessflexible nucleus pulposus, and so changes the load pattern within thedisc, thereby possibly causing delamination of the annulus fibrosus.These changes cause more mechanical instability, thereby causing thecells to emit even more cytokines, typically thereby upregulating MMPs.As this destructive cascade continues and DDD further progresses, thedisc begins to bulge (“a herniated disc”), and then ultimately ruptures,causing the nucleus pulposus to contact the spinal cord and producepain.

US Published Patent Application 2004/0229878 discloses a procedure forthe intradiscal administration of therapeutics, wherein an outer needleand an inner stylet are advanced to the annulus fibrosus, the stylet iswithdrawn and replaced with an inner needle attached to a syringe, andthe inner needle is advanced to the nucleus pulposus for injection ofthe therapeutic into the nucleus pulposus.

In other approaches, a single, fine gauge needle is used to penetratethe skin and musculature approaching the intervertebral disc. However,the drawbacks of this approach include the need for a relatively sturdyneedle and an increase in the risk of infection to the disc (due to thefact that the needle that pierces the skin is also the needle thatenters the disc).

To reduce the risk of infection and subsequent discitis that may resultfrom percutaneous procedures, one common practice is to use a doubleneedle approach in which a larger gauge needle is used to penetrate theskin and a second finer, gauge needle is passed through the first needleand into the intervertebral disc. However, this approach requires twoseparate needles and manual insertion of the second needle inside of thefirst.

Some needle systems developed for use outside of the disc area have dualneedle designs. For example, in needle systems unrelated to intradiscaldelivery of therapeutics, various needle systems and procedures areemployed for aspirating body fluids, and some of these employ concentricmulti-gauge needles. Various access needle systems designed to treatailing tissue are made to allow a second device to pass through an outeraccess needle. Various extendable/retractable needle systems exist assafety devices to prevent user injury by needle sticks.

U.S. Pat. Nos. 5,871,470 and 6,245,044 disclose a set of interlockingconcentric epidural-spinal needles for delivery of medicaments into theepidural and subarachnoid spaces. However, these systems contain twoseparate needles that the user must assemble. Neither system ispre-assembled.

U.S. Pat. Nos. 6,497,686 and 6,695,822 disclose a method and device forperforming sterile endoluminal procedures using a needle system thatincludes two concentric needles. However, these systems do not allow foraspiration of the medicament into an attached syringe. Moreover, thedistal portion of the device is designed to remain in place after theprocedure is completed.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide simple and safepercutaneous access to the intervertebral disc for intradiscal deliveryof therapeutic agents to the disc.

The present inventors have developed a pre-assembled, telescoping needlesystem comprising an outer needle surrounding a finer gauge innerneedle. After percutaneous penetration by the outer needle and itsadvance to the annulus fibrosus, the inner needle is moved distally toextend past the outer needle and penetrate the intervertebral disc. Atherapeutic agent may then be delivered from a syringe through the innerneedle and into the nucleus pulposus.

The needle system of the present invention provides a number ofadvantages over the conventional intradiscal needle systems.

First, the needle system is pre-assembled. This enables both ease of useby the clinician and a reduced diameter of the inner (injection) needle,as it is supported by the outer needle during its insertion at the discsite.

Second, there is a reduced risk of discitis (intradiscal infection). Theinner injection needle is shielded by the outer cannula from contact orexposure to the operative environment, skin and soft inner tissues. Thisreduced exposure yields a reduced infection potential.

Third, the invention provides a controlled discal injection depth. Thepresent invention allows for placement of the tip of the outer needle ator upon the outer rim of the annulus fibrosus, and subsequentadvancement of the inner needle into the disc space. Controlled andmonitored advancement of the inner needle into the disc space allows forpre-determination or measured determination of intradiscal injectiondepths and associated location.

Therefore, in accordance with the present invention, there is provided amethod of delivering a therapeutic agent to an intervertebral dischaving an annulus fibrous and a nucleus pulposus, comprising the stepsof:

-   a) providing a therapeutic delivery system, comprising:    -   i) an outer needle having a distal end, and    -   ii) an inner needle received within the outer needle and having        a distal end,-   b) inserting the outer needle into the patient at a location dorsal    of the intervertebral disc,-   c) advancing the outer needle to abut the annulus fibrosus, and then-   d) advancing only the inner needle into the nucleus pulposus.

DESCRIPTION OF THE FIGURES

FIG. 1A discloses a cross section of the needle system of the presentinvention having a ball detent locking mechanism, prior to itsdeployment into an intervertebral disc.

FIG. 1B is an enlarged cross section of the locking mechanism of FIG.1Aa.

FIG. 2 discloses a cross section of the needle system of FIG. 1A, afterits deployment into an intervertebral disc.

FIG. 3A discloses a cross section of the needle system of the presentinvention having a threaded locking mechanism, prior to its deploymentinto an intervertebral disc.

FIG. 3B is an enlarged cross section of the locking mechanism of FIG.3A.

FIG. 4 discloses a cross section of the needle system of FIG. 3A, afterits deployment into an intervertebral disc.

FIG. 5A discloses a cross section of the needle system of the presentinvention having a keyed locking mechanism, prior to its deployment intoan intervertebral disc.

FIG. 5B is an enlarged cross section of the locking mechanism of FIG.5A.

FIG. 5C is a perspective view of the inner needle of FIG. 5A having achannel herein.

FIG. 6 discloses a cross section of the needle system of FIG. 5A, afterits deployment into an intervertebral disc.

FIGS. 7 a-7 b disclose cross sections of generalized needle systems ofthe present invention.

FIGS. 8 a-8 b disclose cross sections of needle systems of the presentinvention having threaded advancement.

FIGS. 9 a-9 d disclose cross sections of needle systems of the presentinvention having keyed advancement.

DETAILED DESCRIPTION OF THE INVENTION

The present invention comprises a dual needle intradiscal devicecomprising a larger gauge outer needle and a smaller gauge inner needle.Preferably, the needles are sized for intradiscal injection through apercutaneous approach.

The outer needle serves as the access needle, as it functions to pierceand penetration the patient's skin and muscle up to the annulusfibrosus. Further, it functions as a shield for the inner needle priorto its entry into the disc, thereby minimizing the chances of the innerneedle infecting the disc and subsequent discitis. Preferably, the outerneedle has a sufficient stiffness and length to penetrate the skin andunderlying muscle, and is more preferably between 10 gauge and 20 gaugein bore diameter and between 8 cm and 20 cm in length.

The inner needle has a length sufficient to penetrate the annulusfibrosus region of the disc, and is typically between 4 cm and 10 cmlonger than the outer needle. In order to minimize damage to theintervertebral disc, the inner needle should be a fine gauge needle,preferably between 22 gauge and 32 gauge. The proximal end of the innerneedle can attach to a standard syringe.

Preferably, the position of the outer needle can be advanced and thenfixed at various positions along the axis of the inner needle accordingto the needs of the clinician. This is preferably accomplished with alocking mechanism.

For example, in one embodiment, the inner needle is first set in a firstlocked position to extend about 0.5 cm to 1 cm beyond the outer needleso that medicament can be aspirated proximally into the syringe throughthe distal end of the inner needle. Once the medicament has beenaspirated into the syringe, the locking mechanism can be unlocked andthe inner needle retracted and fixed at a new position such it sits 0.5cm to 1 cm proximal to the distal end of the outer needle. In thissecond locked position, the needle system can be inserted through thepatient's skin. When the outer needle has penetrated to a sufficientdepth (such as up to the annulus fibrosus), the locking mechanism canagain be unlocked and the inner needle can slide distally relative tothe outer needle and penetrate the disc.

In some preferred embodiments, the locking mechanism is provided via aball detent mechanism. Now referring to FIGS. 1A and 1B, in someembodiments, there is provided a needle system 1 for intradiscaldelivery of a therapeutic agent, comprising:

-   -   a) an outer needle 3 having an outer surface 5 having a        transverse throughhole 7, and a detent 9 provided in the        throughhole, the detent having a projection 11 extending        inwardly, and    -   b) an inner needle 13 having an outer surface 15 having a        plurality of axially spaced grooves 17, wherein the projection        of the detent is shaped to be received in the plurality of        axially spaced grooves.

In some embodiments thereof, the outer surface of the outer needle has ahole therein into which a pushbutton detent is releasably provided. Theouter surface of the inner needle contains a plurality of grooves spacedat predetermined intervals. When the push button of the outer needle isengaged with groove of the inner needle, the needle system is locked andthe relative axial positions of the two needles are fixed. When the pushbutton of the outer needle is disengaged from a groove of the innerneedle, the system is unlocked and the inner needle may be moved forwardor backward relative to the outer needle (or vice versa). FIG. 2 showsthe distal movement of the inner needle 13 by a single stop interval ascompared to its position in FIG. 1A.

In some preferred embodiments, the locking mechanism is provided via apair of mating threads. In these embodiments, the inner needle can bethreadably connected to the outer needle and advanced to a desired depthin the disc by rotation of the inner needle within the outer needle. Nowreferring to FIGS. 3A and 3B, in some embodiments, there is provided aneedle system 21 for intradiscal delivery of a therapeutic agent,comprising:

-   -   a) an outer needle 23 having an inner surface 25 having a first        thread 27, and    -   b) an inner needle 31 having an outer surface 33 having a second        thread 35, wherein the first thread is adapted to mate with the        second thread.

When one of the needles is rotated in respect to the other needle, therelative rotation of the engaged threads is such that axial movement ofthe inner needle is accomplished.

FIG. 4 shows the distal movement of the inner needle produced byrelative rotation of the threads, as compared to its position in FIG.3A.

Now referring to FIG. 5A-5C, in some embodiments, the stops are providedby a keyed mechanism. In FIGS. 5A-5C, there is provided a needle system51 for intradiscal delivery of a therapeutic agent, comprising:

-   -   a) an outer needle 61 having an inner surface 63 having a tab 65        extending therefrom, and    -   b) an inner needle 71 having an outer surface 73 having a        channel 75 therein, wherein the tab is received in the channel.

In preferred embodiments thereof, the inner diameter of the outer needlehas a tab extending therefrom, while the outer diameter of the innerneedle has a channel therein, wherein the channel has alternating axialand lateral portions defining a plurality of stop intervals. In use, theclinician moves the inner needle distally until the tab of the outerneedle abuts the lateral portion of the inner needle. If the cliniciandesires to move the inner needle distally again, the clinician rotatesthe inner needle so that the tab moves along the lateral portion of thechannel and enters the next axial portion of the channel. The clinicianthen moves the inner needle axially once again, with the channel of theinner needle being guided by the tab, until the tab of the outer needleabuts the next lateral portion of the inner needle.

FIG. 6 shows the distal movement of the inner needle produced bymovement of the tab in the channel, as compared to its position in FIG.5A.

In other embodiments using a keyed locking mechanism, the inner surfaceof the outer needle has the channel and the outer surface of the innerneedle has the tab. In one preferred embodiment, the keyed lockingmechanism includes a simple twist-lock mechanism such that in twopredetermined rotational positions (e.g., 0° and either 45°, 90°, 180°,or 270°), the outer needle can slide relative to the inner needle.

In some embodiments using a locking mechanism, and now referring to FIG.1A, the inner needle has a first proximal outer diameter 81 and a seconddistal outer diameter 83, wherein the first proximal outer diameter isgreater than the second distal outer diameter. This embodiment minimizesthe diameter of the portion of the needle that penetrates the annulusfibrosus, thereby reducing injury to the annulus fibrosus. In someembodiments thereof, the system further comprises an annular plug 85disposed within the distal end of the outer needle and adapted to fitbetween the inner and outer needles. The annular plug prevents fluidfrom entering the bore of the outer needle when the inner needle has areduced diameter and provides a guide for the distal advance of theinner needle. In this embodiment, the first proximal outer diameter ispreferably sized to be slightly less than the inner diameter of theouter needle, so that the locking mechanism (whether it be a ball detentmechanism, a pair of threads, or a keyed mechanism) possesses a snugfit.

In some embodiments, after the medicament is administered, the lockingmechanism can be re-engaged and the two needles can be removed togetherfrom the patient. In other embodiments, after the medicament isadministered, the locking mechanism remains disengaged and the twoneedles are removed independently.

In some embodiments wherein only the inner needle is removed, a secondneedle can be inserted through the same outer needle. In someembodiments thereof, this second inner needle may be a standard needlethat does not lock to the outer needle. In other embodiments thereof,this second inner needle may comprise a locking feature that isengageable with a locking feature of the outer needle.

In some embodiments, depth markings can be provided to allow theclinician to measure the depth of discal entry and location of thetreatment within the nucleus pulposus, and thereby control the depth ofdiscal entry and location of the treatment within the nucleus pulposus.

The needle system of the present invention can be suitably used toinject therapeutic agents into intravertebral disc and synovial joints(such as facet joints, hip joints and knee joints). It may be used inthe aspiration of bone marrow or for biopsy procedures.

In some embodiments, the therapuetic materials disclosed in US PublishedPatent Application 2004/0229878, which is incorporated by reference inits entirety, are injected into the disc.

FIGS. 7 a and 7 b depict the general concept of the IntervertebralPuncture and Treatment System in its respective pre-insertion andpost-insertion modes. During pre-insertion, and now referring to FIG. 7a, the tips of the outer cannula 101 and inner needle 103 are alignedand advanced until disc contact is observed. In some embodimentsthereof, the outer cannula is about 18 gauge RW, with a 0.033 inch IDand a 0.050 inch OD, while the inner delivery needle is about 22 gaugeRW, with a 0.016 inch ID and a 0.028 inch OD. Also shown is ageneralized representation of a depth control means 105 (that is enabledin subsequent figures by threaded advancement and keyway stops). Depthcontrol markings 107 correspond to the insertion depth (×mm) into thedisc following contact with the annular wall, as can be seen in thepost-insertion image FIG. 7 b.

Now referring to FIG. 8 a, there is provided a more detailed embodimentdepicted device orientation pre-insertion into the disc. This device hasa threaded advancement means 110 and a positive depth stop 111 (as shownby ghost threads) at an insertion depth of ×mm. Handles 113 are providedon each of the outer cannula 115 and inner needle 117 to assist inthreading the inner needle into the outer cannula. Also shown in thisFIG. 8 a is the treatment attachment location 119 (which may be, forexample, a luer slip, luer lock, or injection cap) at which the deviceis attached to a treatment container 120 (which may be, for example, asyringe, vial, bag, or pouch).

FIG. 8 b discloses the threaded advancement device of FIG. 8 a followinginsertion into the disc. In this case, threaded advancement of the innerneedle has been stopped by the positive depth stop 111 (provided by theend of the threads) at a predetermined depth of ×mm. Also shown in thisfigure are handles 113, outer cannula 115, inner needle 117, and thetreatment container 120 attached to the inner needle 117 at treatmentattachment location 119 for dispensing at desired depth.

Now referring to FIGS. 9 a and 9 b, there is provided a device having anouter cannula 121, an inner needle 123, advancement handles 125, atreatment container 127 attached to the inner needle at a treatmentlocation 129, and keyed advancement means 131 in its pre-insertionconfiguration. The key 133 is located on either the outer and innerneedle (shown here on the inner needle as a protrusion) and is disposedwithin keyway 135. The distance between the key and the keyway stop 137will control the depth of intradiscal insertion (2×mm) following contactwith the annulus.

Now referring to FIGS. 9 c and 9 d, there is provided the device ofFIGS. 9 a and 9 b in its post-insertion configuration. In this case,inner needle 123 and its accompanying key 133 have been advanced untilthe keyway stop is contacted (×mm). Additional advancement of the innerneedle (for example, 2×mm) may be obtained by rotating the inner needle(for example, 90 degrees) and applying an advancement force until thesecond key way stop is contacted.

EXAMPLE I

This non-limiting prophetic example describes how to transdiscallyadminister a formulation comprising a therapeutic agent and saline intoa nucleus pulposus of a degenerating disc.

First, a clinician uses a diagnostic test to verify that a particulardisc within a patient has high levels of a particular pro-inflammatorycytokine.

Next, the clinician provides a local anesthetic (such as 5 ml lidocaine)to the region dorsal of the disc of concern to reduce subcutaneous pain.

Next, the clinician punctures the skin of the patient dorsal the disc ofconcern with a relatively large (e.g., 18-19 gauge) needle having asmaller gauge needle contained therein, and advances the needle throughsubcutaneous fat and dorsal sacrolumbar ligament and muscles to theouter edge of the intervertebral disc. The proximal end opening of thesmaller needle is fluidly connected to a syringe. The barrel of thesyringe contains the formulation of the present invention. Theformulation contains REMICADE® infliximab, and has an infliximabconcentration of between about 30 mg/ml and about 60 mg/ml.

Next, the physician advances the smaller needle co-axially through thelarger needle and past the distal end of the larger needle, therebypuncturing the annulus fibrosus. The smaller needle is then furtheradvanced into the center of the nucleus pulposus. Finally, the clinciandepresses the plunger of the syringe, thereby injecting between about0.1 and 1 ml of the formulation into the nucleus pulposus.

1. A method of delivering a therapeutic agent to a patient having anintervertebral disc having an annulus fibrous and a nucleus pulposus,comprising the steps of: a) providing a therapeutic delivery system,comprising: i) an outer needle having a distal end, and ii) an innerneedle received within the outer needle and having a distal end, b)inserting the outer needle into the patient at a location dorsal of theintervertebral disc, c) advancing the outer needle to abut the annulusfibrosus, and d) advancing only the inner needle into the nucleuspulposus.
 2. The method of claim 1 wherein the inner needle has an outersurface having i) a first proximal outer diameter, and ii) a seconddistal outer diameter, wherein the first proximal outer diameter isgreater than the second distal outer diameter.
 3. The method of claim 1wherein the delivery system further comprises: iii) a syringe in fluidconnection with the inner needle, wherein the syringe contains atherapeutic agent.
 4. The method of claim 3 further comprising the stepof: e) actuating the syringe to inject the therapeutic agent into thenucleus pulposus.
 5. The method of claim 3 further comprising the stepof: e) removing the inner needle from the outer needle, and f) insertinga second inner needle into the outer needle.
 6. A needle system fordelivery of a therapeutic agent, comprising: a) an outer needle havingan outer surface having a transverse throughhole, and a detent providedin the throughhole, the detent having a projection extending inwardly,and b) an inner needle having an outer surface having a plurality ofaxially spaced grooves, wherein the projection of the detent is shapedto be received in the plurality of axially spaced grooves.
 7. The systemof claim 6 wherein the outer surface of the inner needle has a firstproximal outer diameter upon which the grooves are located and a seconddistal outer diameter, wherein the first proximal outer diameter isgreater than the second distal outer diameter.
 8. The system of claim 7wherein the system further comprises: c) an annular plug disposed withina distal end of the outer needle and adapted to fit between the innerand outer needles.
 9. The system of claim 6 further comprising: c) asyringe in fluid connection with the inner needle, wherein the syringecontains a therapeutic agent.
 10. The system of claim 6 wherein thesystem is pre-assembled.
 11. The system of claim 6 wherein the outersurface of the inner needle has a plurality of depth markings.
 12. Aneedle system for delivery of a therapeutic agent, comprising: a) anouter needle having an inner surface having a first thread, and b) aninner needle having an outer surface having a second thread, wherein thefirst thread is adapted to mate with the second thread.
 13. The systemof claim 12 wherein the outer surface of the inner needle has a firstproximal outer diameter upon which the second thread is located and asecond distal outer diameter, wherein the first proximal outer diameteris greater than the second distal outer diameter.
 14. The system ofclaim 13 wherein the system further comprises: c) an annular plugdisposed within a distal end of the outer needle and adapted to fitbetween the inner and outer needles.
 15. The system of claim 12 furthercomprising: c) a syringe in fluid connection with the inner needle,wherein the syringe contains a therapeutic agent.
 16. The system ofclaim 12 wherein the system is pre-assembled.
 17. The system of claim 12wherein the outer surface of the inner needle has a plurality of depthmarkings.
 18. A needle system for delivery of a therapeutic agent,comprising: a) an outer needle having an inner surface, and b) an innerneedle having an outer surface, wherein one of the needles has a tabextending from its surface, the other needle has a channel in itssurface, and wherein the tab is received in the channel.
 19. The needlesystem of claim 18 wherein the channel has a plurality of alternatingaxial portions and lateral portions.
 20. The needle system of claim 18wherein the inner surface of the outer needle has the tab and the outersurface of the inner needle has the channel.
 21. The needle system ofclaim 18 wherein the inner surface of the outer needle has the channeland the outer surface of the inner needle has the tab.
 22. The system ofclaim 18 wherein the outer surface of the inner needle has a firstproximal outer diameter upon which the tab or channel is located and asecond distal outer diameter, wherein the first proximal outer diameteris greater than the second distal outer diameter.
 23. The system ofclaim 22 wherein the system further comprises: c) an annular plugdisposed within a distal end of the outer needle and adapted to fitbetween the inner and outer needles.
 24. The system of claim 18 furthercomprising: c) a syringe in fluid connection with the inner needle,wherein the syringe contains a therapeutic agent.
 25. The system ofclaim 18 wherein the system is pre-assembled.
 26. The system of claim 18wherein the outer surface of the inner needle has a plurality of depthmarkings.